Epithelial cell sheets have an important role in compartmentalizing various tissues and maintaining their local homeostasis via intercellular barriers consisting of tight junctions (TJs) and in determining the morphogenesis of organs and regulating their functions.
TJs are barrier forming cell-cell junctions that are found in a variety of cell types and tissues, and regulate the barrier activity or permeability of solutes through epithelial cell sheets. Four distinct types of integral membrane proteins have been shown to localize at TJs: occludin, junctional adhesion molecules, claudins, and tricellulin.
Claudins, the major components of tight junction (TJ) strands, which form paracellular barriers, consist of at least 24 family members in mice and humans and now are believed to predominantly constitute functional TJ strands. Evidence has been accumulated that combinations of claudins determine the specific properties of the barrier regarding paracelluar permeability between cells.
Recent functional analyses of claudins in cell cultures and in mice have suggested that claudin-based TJs may have pivotal functions in the regulation of the epithelial microenvironment, which is critical for various biological functions such as control of cell proliferation.
It is reported that continuous Claudin-based TJs occur in the epidermis and Claudin-based tight junctions are crucial for the barrier function of the mammalian skin (J Cell Biol. 2002 Mar. 18; 156(6), 1099-1111, the cited reference is herein incorporated by reference).
Claudin-15 is a type of claudin expressed in many organs of mice in different combinations with other types of claudins. The inventor reported that claudin-15-based formation of TJs to organize the microenvironment including ion conductance is important for normal-sized morphogenesis of the small intestine (Gastroenterology 2008; 134:523-534, the cited reference is herein incorporated by reference).
Prostaglandins (hereinafter, referred to as PG(s)) are fatty acid derivatives, members of class of organic carboxylic acids, which are contained in tissues or organs of human or other mammals, and exhibit a wide range of physiological activity. PGs found in nature (primary PGs) generally have a prostanoic acid skeleton as shown in the formula (A):

On the other hand, some of synthetic analogues of primary PGs have modified skeletons. The primary PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PCJs according to the structure of the five-membered ring moiety, and further classified into the following three types by the number and position of the unsaturated bond at the carbon chain moiety:
Subscript 1: 13,14-unsaturated-15-OH
Subscript 2: 5,6- and 13,14-diunsaturated-15-OH
Subscript 3: 5,6-, 13,14-, and 17,18-triunsaturated-15-OH.
Further, the PGFs are classified, according to the configuration of the hydroxyl group at the 9-position, into α type (the hydroxyl group is of an α-configuration) and β type (the hydroxyl group is of a β-configuration).
PGs are known to have various pharmacological and physiological activities, for example, vasodilatation, inducing of inflammation, platelet aggregation, stimulating uterine muscle, stimulating intestinal muscle, anti-ulcer effect and the like.
Some 15-keto (i.e., having oxo at the 15-position instead of hydroxy)-PGs and 13,14-dihydro (i.e., having single bond between the 13 and 14-position)-15-keto-PGs are fatty acid derivatives known as the substances naturally produced by the action of enzymes during the metabolism of primary PGs.
U.S. Patent application publication No. 2006/0281818 to Ueno et al. (the cited reference is herein incorporated by reference) describes that a specific prostaglandin compound has a significant effect on a conformational change in the TJs that results in recovery of gastrointestinal mucosal barrier function.